Abstract
Summary BackgroundVariceal bleeding, one of the major complications of liver cirrhosis, is primarily due to platelet activation defect and secondarily due to coagulation defects. Platelet adhesion is the key event in hemostasis. Since nitric oxide (NO) related stress is known to influence platelet functions in liver cirrhosis, we undertook the present study to evaluate the possible mechanism involved in the inhibition of platelet adhesion by NO.Methods:Agonist-induced platelet adhesion in vitro was measured in platelets isolated from normal subjects and cirrhosis patients. The time-dependent changes in nitric oxide synthase (NOS), NO, 3',5'-cyclic guanosine monophosphate (cGMP) and cytosolic calcium (Ca2+) levels were monitored during adhesion. The percentage of platelet adhesion was also monitored in the presence of an eNOS inhibitor and a cGMP inhibitor.Results:The percentage of adhesion was significantly lower in cirrhosis platelets. Time-dependent changes in the cGMP NO and NOS level in platelets stimulated with collagen were significantly high, with a significantly low level of elevation of cytosolic Ca2+in cirrhosis as adhesion proceeded. The results showed improved platelet adhesion with inhibitors of NOS and cGMP with concomitant elevation in Ca2+level.Conclusions:It is inferred that elevation in the formation of cGMP due to stimulation of NOS activity inhibits Ca2+mobilization from the internal store, an essential process to trigger platelet activation. The abnormal alterations were significantly lower in cirrhosis patients without bleeding complications. So, it could be stated that the bleeding abnormality in liver cirrhosis might be due to defective platelet adhesion influenced by the NO-cGMP pathway.
Highlights
Blood platelets play a major role in hemostasis
It could be stated that the bleeding abnormality in liver cirrhosis might be due to defective platelet adhesion influenced by the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway
When platelets were activated with 20 mg/mL collagen significantly lower level (p
Summary
Blood platelets play a major role in hemostasis They respond to vascular injury by forming a hemostatic plug through a complex process involving adherence of platelets to the endothelium, activation, and recruitment of more platelets and release of procoagulants [1,2,3,4,5,6]. At the site of injury, platelets come into contact and adhere to the subendothelial tissues with the help of von Willebrand factor, forming bridges between the platelet surface glycoprotein Ib and the components of the subendothelium. This continues with the attachment of platelet receptors to several adhesive proteins in the matrix of connective tissue. Other platelets spread, covering the collagen surface with a single layer of platelets in a similar fashion, forming a plug to seal off the injured tissue [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
